This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Mitochondria are the organelles responsible for oxidative phosphorylation. The efficiency and regulation of oxidative metabolism is critical to sustain different physiological processes. Mitochondrial deficiencies that affect oxidative metabolism are linked to aging, neurodegeneration and a variety of genetic mitochondrial diseases. Mitochondrial function is strictly dependent on the expression of the mitochondrial genome, and mitochondrial gene transcription is a key link in this process. Our laboratory is currently trying to understand the structural biology and biochemistry of the mitochondrial transcription machinery and to study its control by nuclear hormone receptors. Elucidating the mechanisms of regulation of this key cellular process has important implications for a number of human diseases and may lead to new potential avenues for therapeutics.